Abstract
DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water-soluble platinum compound which posses minimal cross-resistance to cisplatin and shows relatively less side effects. In an attempt to establish whether the combination of DPR with other conventional anticancer drugs would be of any benefit we assessed in vitro the cytotoxic effects of combinations of DPR with the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX), and the intercalating agent of the anthracycline group doxorubicin (DOX) on murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells. These agents were selected because of their common use in the clinic and because they represent four distinct categories of antineoplastic mechanisms. Cells were incubated for 72 h in the presence of single or combined drugs, and the cytotoxic effect was determined by the MTT assay. The analysis of combination treatment was made by the isobole method. In human A2780 cells, an overall synergy was found for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also observed for most combinations with MTX or MMC. A DPR concentration-dependent additivity and antagonism was seen at the highest MTX concentration (1 μM), while additive effects were observed for the combined treatments of DPR and low concentrations of MMC (0.008 and 0.0016 μM) Additive effects were also observed for the association of DPR and TAX over most combinations tested. In murine M5076 cells, synergism was the prevailing result observed when DPR was combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we observed additivity over most combinations tested. These findings suggest that DPR, when simultaneously administered with standard anticancer agents, may be advantagious for cyto-killing.
| Original language | English |
|---|---|
| Pages (from-to) | 457-463 |
| Number of pages | 7 |
| Journal | Anti-Cancer Drugs |
| Volume | 9 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1998 |
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Keywords
- Anticancer drugs
- DPR
- In vitro assay
- Synergism
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Pharmacology
Cite this
Combination of cisplatin-procaine complex DPR with anticancer drugs increases cytotoxicity against ovarian cancer cell lines. / Viale, Maurizio; Pastrone, Ilaria; Pellecchia, Caterina; Vannozzi, Maria O.; Cafaggi, Sergio; Esposito, Mauro.
In: Anti-Cancer Drugs, Vol. 9, No. 5, 1998, p. 457-463.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combination of cisplatin-procaine complex DPR with anticancer drugs increases cytotoxicity against ovarian cancer cell lines
AU - Viale, Maurizio
AU - Pastrone, Ilaria
AU - Pellecchia, Caterina
AU - Vannozzi, Maria O.
AU - Cafaggi, Sergio
AU - Esposito, Mauro
PY - 1998
Y1 - 1998
N2 - DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water-soluble platinum compound which posses minimal cross-resistance to cisplatin and shows relatively less side effects. In an attempt to establish whether the combination of DPR with other conventional anticancer drugs would be of any benefit we assessed in vitro the cytotoxic effects of combinations of DPR with the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX), and the intercalating agent of the anthracycline group doxorubicin (DOX) on murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells. These agents were selected because of their common use in the clinic and because they represent four distinct categories of antineoplastic mechanisms. Cells were incubated for 72 h in the presence of single or combined drugs, and the cytotoxic effect was determined by the MTT assay. The analysis of combination treatment was made by the isobole method. In human A2780 cells, an overall synergy was found for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also observed for most combinations with MTX or MMC. A DPR concentration-dependent additivity and antagonism was seen at the highest MTX concentration (1 μM), while additive effects were observed for the combined treatments of DPR and low concentrations of MMC (0.008 and 0.0016 μM) Additive effects were also observed for the association of DPR and TAX over most combinations tested. In murine M5076 cells, synergism was the prevailing result observed when DPR was combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we observed additivity over most combinations tested. These findings suggest that DPR, when simultaneously administered with standard anticancer agents, may be advantagious for cyto-killing.
AB - DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-aminobenzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water-soluble platinum compound which posses minimal cross-resistance to cisplatin and shows relatively less side effects. In an attempt to establish whether the combination of DPR with other conventional anticancer drugs would be of any benefit we assessed in vitro the cytotoxic effects of combinations of DPR with the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX), and the intercalating agent of the anthracycline group doxorubicin (DOX) on murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells. These agents were selected because of their common use in the clinic and because they represent four distinct categories of antineoplastic mechanisms. Cells were incubated for 72 h in the presence of single or combined drugs, and the cytotoxic effect was determined by the MTT assay. The analysis of combination treatment was made by the isobole method. In human A2780 cells, an overall synergy was found for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also observed for most combinations with MTX or MMC. A DPR concentration-dependent additivity and antagonism was seen at the highest MTX concentration (1 μM), while additive effects were observed for the combined treatments of DPR and low concentrations of MMC (0.008 and 0.0016 μM) Additive effects were also observed for the association of DPR and TAX over most combinations tested. In murine M5076 cells, synergism was the prevailing result observed when DPR was combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we observed additivity over most combinations tested. These findings suggest that DPR, when simultaneously administered with standard anticancer agents, may be advantagious for cyto-killing.
KW - Anticancer drugs
KW - DPR
KW - In vitro assay
KW - Synergism
UR - http://www.scopus.com/inward/record.url?scp=0031846776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031846776&partnerID=8YFLogxK
U2 - 10.1097/00001813-199806000-00013
DO - 10.1097/00001813-199806000-00013
M3 - Article
VL - 9
SP - 457
EP - 463
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
SN - 0959-4973
IS - 5
ER -